Abstract
Conditioned pain modulation (CPM) describes the reduction in pain evoked by a test stimulus (TS) when presented together with a heterotopic painful conditioning stimulus (CS). CPM has been proposed to reflect inter-individual differences in endogenous pain modulation, which may predict susceptibility for acute and chronic pain. Here, we aimed to estimate the relative variance in CPM explained by inter-individual differences compared to age, sex, and CS physical and pain intensity. We constructed linear and mixed effect models on pooled data from 171 participants of several studies, of which 97 had repeated measures. Cross-sectional analyses showed no significant effect of age, sex or CS intensity. Repeated measures analyses revealed a significant effect of CS physical intensity (p = 0.002) but not CS pain intensity (p = 0.159). Variance decomposition showed that inter-individual differences accounted for 24% to 34% of the variance in CPM while age, sex, and CS intensity together explained <3% to 12%. In conclusion, the variance in CPM explained by inter-individual differences largely exceeds that of commonly considered factors such as age, sex and CS intensity. This may explain why predictive capability of these factors has had conflicting results and suggests that future models investigating them should account for inter-individual differences.
Highlights
Conditioned pain modulation (CPM) paradigms measure the component of human endogenous pain inhibition underlying the “pain inhibits pain” phenomenon [1], based on a noxious test stimulus (TS) being perceived as less painful if presented in combination with a painful heterotopic conditioning stimulus (CS)
There was no significant relation of age, sex or CPM paradigm with the CPM effect
We found no difference in CPM effect between men and women, which is consistent with some previous findings [37,38], but larger CPM effects in men compared to women have been reported [6,39]
Summary
Conditioned pain modulation (CPM) paradigms measure the component of human endogenous pain inhibition underlying the “pain inhibits pain” phenomenon [1], based on a noxious test stimulus (TS) being perceived as less painful if presented in combination with a painful heterotopic conditioning stimulus (CS). CPM magnitude is reduced in a variety of chronic pain conditions, pointing towards dysregulation of endogenous pain inhibition in these patients [2]. Individual differences in CPM are considerable, and have been proposed to predict susceptibility to acute and chronic pain [3,4]. An effect of pre-existing psychological factors has been discussed, but a recent study has not shown a clear relation to the CPM effect [9]. It is currently not known how much individual variance remains after accounting for the effects of age and sex
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